Oncologists have identified five diverse subtypes of epithelial ovarian cancers: epithelial ovarian cancers as high-grade serous, endometrioid, clear-cell, mucinous, or low-grade serous. The subtypes differ in clinical characteristics, such as tissue of origin and molecular biology, and prognostic values, such as response to treatment and outcome.
Low-grade serous ovarian carcinoma (LGSOC) is a rare type of ovarian cancer accounting for less than 10% of all ovarian cancers. LGSOC cases are often diagnosed in younger women (under 60 years). While this type of cancer is typically slow growing, it also tends to be resistant to chemotherapy.
The Phase 2/3 multicenter, open-label trial was conducted internationally at 84 hospitals across the USA and UK to test the efficacy of MAPK inhibitor called trametinib. Patients recruited for the study were at least 18 years of age when diagnosed with LGSOC. The researchers randomly assigned patients to one of two treatment groups: trametinib or standard-of-care. options for women diagnosed with LGSOC.
One common characteristic of many cases of LGSOC is mutations in the Mitogen-Activated Protein Kinase (MAPK) pathway, which regulates proliferation, survival, and apoptosis in cancer cells. These findings have generated interest in targeting the MAPK pathway for the treatment of LGSOC. The promising results of one Clinical Trial (NCT02101788) studying such a therapeutic approach were recently published in The Lancet.
The Phase 2/3 multicenter, open-label trial was conducted internationally at 84 hospitals across the USA and UK to test the efficacy of MAPK inhibitor called trametinib. Patients recruited for the study were at least 18 years of age when diagnosed with LGSOC. The researchers randomly assigned patients to one of two treatment groups: trametinib or standard-of-care. Because this was a large-scale study conducted in multiple countries, the standard-of-care differed between participating centers. Patients in the standard-of-care group received one of five chemotherapy treatments: paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole, or tamoxifen.
Once enrolled and assigned to a treatment group, doctors imaged tumors before the first treatment and every eight weeks for the first fifteen months. After this, the time between imaging was reduced to every three months.
The Clinical Trial enrolled 260 patients assigning 130 to each treatment group. Median progression-free survival, the time from randomization to disease progression or death, was 13 months in the trametinib group and about seven months in the standard-of-care group. Further, the objective response rate, the proportion of patients with a clinical response, in the trametinib group was 26% compared to 6% in the standard-of-care group.
The results of this Clinical Trial suggest that oncologists should consider trametinib for the treatment of women with LGSOC. Further, trametinib could become a the standard-of-care treatment for this type of cancer.
Sources: Hum Path, Can Biol Med, Cancer Network, Obstet Gynecol, Reprod Biol Endocrinol, The Lancet